Synthesis of conformationally constrained benzoylureas as BH3-mimetics
- Author(s)
- Brady, RM; Hatzis, E; Connor, T; Street, IP; Baell, JB; Lessene, G;
- Details
- Publication Year 2012,Volume 10,Issue #27,Page 5230-5237
- Journal Title
- ORGANIC & BIOMOLECULAR CHEMISTRY
- Publication Type
- Journal Article
- Abstract
- The design of small molecules that mimic the BH3 domain and bind to Bcl-2 proteins has emerged as a promising approach to discovering novel anti-cancer therapeutics. We reveal the design and synthesis of conformationally constrained benzoylurea scaffolds as conformational probes. Central to helix mimicry, the intramolecular hydrogen bond in the benzoylurea plays a key role in the pre-organisation of the acyclic substrates for cyclisation via ring closing metathesis, providing efficient access to the constrained mimetics.
- Publisher
- ROYAL SOC CHEMISTRY
- Keywords
- OXYGEN CHANNELING ASSAY; CELL-SURVIVAL; APOPTOSIS; BCL-2; COMPLEX; FAMILY; REGULATORS; SWITCH
- Publisher's Version
- https://doi.org/10.1039/c2ob25618e
- Terms of Use/Rights Notice
- © Royal Society of Chemistry 2013
Creation Date: 2012-01-01 12:00:00